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To determine minimally clinically important differences (MCIDs) for Disability Rating Scale (DRS), Fugl-Meyer Upper Extremity Subscale (FM-UE), Fugl-Meyer Lower Extremity Subscale (FM-LE), and Fugl-Meyer Motor Scale (FMMS) in patients with chronic motor deficits secondary to traumatic brain injury (TBI).Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N = 61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells. MCIDs for DRS, FM-UE, FM-LE, and FMMS were triangulated with distribution-based, anchor-based, and Delphi panel estimates.Triangulated MCIDs were: 1) -1.5 points for the Disability Rating Scale; 2) 6.2 points for the Fugl-Meyer Upper Extremity Subscale; 3) 3.2 points for the Fugl-Meyer Lower Extremity Subscale; and 4) 8.4 points for the Fugl-Meyer Motor Scale.For the first time in the setting of patients with chronic motor deficits secondary to TBI, this study reports triangulated MCIDs for: 1) DRS, a measure of global outcome; and 2) Fugl-Meyer Scales, measures of motor impairment. These findings guide the use of DRS and Fugl-Meyer Scales in the assessment of global disability outcome and motor impairment in future TBI clinical trials.

Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

ObjectiveTo determine whether chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow–derived mesenchymal stromal/stem cells (SB623).MethodsThis 6-month interim analysis of the 1-year double-blind, randomized, surgical sham–controlled, phase 2 Stem Cell Therapy for Traumatic Brain Injury (STEMTRA) trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multicenter trial (n = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, or 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (n = 61), and efficacy was assessed in the modified intent-to-treat population of randomized patients who underwent surgery (n = 61; SB623 = 46, control = 15).ResultsThe primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (least square [LS] mean) 8.3 (standard error 1.4) vs 2.3 (standard error 2.5) for control at 6 months, the LS mean difference was 6.0 (95% confidence interval 0.3–11.8, p = 0.040). Secondary efficacy endpoints improved from baseline but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25).ConclusionsSB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls.ClinicalTrials.gov Identifier:NCT02416492.Classification of EvidenceThis study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.

Recent advances in stroke treatment have targeted acute and subacute stroke with therapies administered in the first 48 hours after onset. Current treatment options focus on dissolution of thrombus via the use of a tissue-type plasminogen activator within 4.5 hours (eg, alteplase), or mechanical thrombectomy within 6 hours of stroke onset.1–3 However, both of these approaches are applicable to limited numbers of stroke patients and not all patients achieve good outcomes.4 Although the pathology of acute stroke is well described, the time course for recovery is not. Most return of function after stroke occurs early and evidence suggests that recovery plateaus 3 to 6 months after stroke onset.5 For the purposes of this article, chronic stroke will be defined as 6 months to years after onset. At this point, liquefaction of damaged tissue should be complete resulting in a fluid-filled cyst. Behavioral recovery tends to plateau during this period revealing the likely scale of permanent disability.6,7 In the United States, 795 000 people experience a new or recurrent stroke each year, with the prevalence of stroke estimated to be 7.2 million cases during 2014 in patients >20 years of age.8 Current therapeutic approaches have not yielded significant benefits for patients with chronic stroke. Incorporation of physical therapy programs to help augment recovery in motor function in the days to weeks after stroke may be of limited use.9 Transcranial magnetic stimulation has been investigated, however, there is no definitive evidence of efficacy with this approach.10,11 Administration of catecholamine agonists (eg, amphetamine) or ion channel mediators (dalfampridine) have not been reported to be effective.12–15 Enhancing the generation of endogenous stem cells via the administration of granulocyte colony-stimulating factor has not been successful in improving outcomes.16 Studies …

Ryk is a member of the receptor tyrosine kinase (RTK) family of proteins that control and regulate cellular processes. It is distinguished by binding Wnt ligands and having no detectable intrinsic protein tyrosine kinase activity suggesting Ryk is a pseudokinase. Here, we show an essential role for Ryk in directing morphogenetic events required for normal cardiac development through the examination of Ryk-deficient mice. We employed vascular corrosion casting, vascular perfusion with contrast dye, and immunohistochemistry to characterize cardiovascular and pharyngeal defects in Ryk-/- embryos. Ryk-/- mice exhibit a variety of malformations of the heart and outflow tract that resemble human congenital heart defects. This included stenosis and interruption of the aortic arch, ventriculoarterial malalignment, ventricular septal defects and abnormal pharyngeal arch artery remodelling. This study therefore defines a key intersection between a subset of growth factor receptors involved in planar cell polarity signalling, the Wnt family and mammalian cardiovascular development.

OBJECTIVEThe aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow–derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke.METHODSThis was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance.RESULTSA total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4–10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, −2.1 (95% CI −3.3 to −1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9–29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0–16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1–2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (−0.735, p < 0.01) scores at 24 months.CONCLUSIONSIn this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.Clinical trial registration no.: NCT01287936 (clinicaltrials.gov)

Generation of site-appropriate tissue in the oral cavity includes the restoration of the correct anatomic type, amount, and distribution of the tissue. This study is a post hoc analysis of data collected during previously published results from two randomized clinical trials of a living cellular sheet (LCS; allogenic cultured keratinocytes and fibroblasts in bovine collagen) versus a free gingival graft (FGG), evaluating their ability to augment keratinized tissue or gingiva.Post hoc histologic and clinical (photographic) comparisons of the outcomes of treatment were performed on histologic and photographic data gathered in the two randomized clinical trials.Histologic findings showed that LCS-treated sites resembled gingiva rather than alveolar mucosa. Photographic analysis indicated that LCS treatment resulted in more site-appropriate tissue than FGG in terms of tissue color, with adjacent untreated tissue, absence of scar formation or keloid-like appearance, and mucogingival junction alignment.Treatment of mucogingival defects with LCS resulted in the generation of tissue that is more site appropriate than tissue transplanted from the palate.

We thank Dr Clark for his comments. Immunomodulation related to protein and molecular factors secreted by the SB623 cells could be one of the mechanisms underlying the observed neurological recovery in our patients1 and could suggest that there is ongoing chronic inflammation >6 months after stroke that is suppressing intact neural circuits and rendering them nonfunctional. This concept has some support in the recent preclinical and clinical literature.2 In addition, it is conceivable that the transplanted SB623-secreted factors are enhancing native neurogenesis or synaptogenesis, potentially through blocking excess tumor necrosis factor effects after stroke, although this is unproven. It will be important …

Clinical applications of mesenchymal stromal cells (MSCs) require the manufacture of large cell lots, which involves multiple passages for cell expansion and sometimes genetic modification. MSCs from various sources, including bone marrow (BM), exhibit high donor-to-donor variability in their growth characteristics. This can lead to unpredictable manufacturing outcomes with respect to success or failure of individual lots. Early determination of lot success has the potential to reduce the cost and improve the efficiency of the MSC manufacturing process. However, methods that effectively predict lot growth potential early in the manufacturing process are currently lacking. Here we report that the growth potential of an MSC lot can be predicted a few days after BM plating based on α-smooth muscle actin (αSMA) protein expression in large colony-forming unit-fibroblast (CFU-f) colonies. The proposed prediction method could be a useful tool to prospectively determine MSC lot success or failure.

Oral soft tissue plays an important role in the structure and function of the oral cavity by protecting against exogenous substances, pathogens, and mechanical stresses. Repair of oral soft tissue defects that arise as a result of disease, trauma, or congenital abnormalities is often accomplished via transplantation or transfer of autologous mucosal tissue. However, this method of treatment can be complicated by the relatively small amount of autologous mucosal tissue that is available, as well as by the morbidity that may be associated with the donor site and patient reluctance to have oral (eg, palatal) surgery. To circumvent these problems, clinicians have turned to the fields of tissue engineering and regenerative medicine to develop acellular and cellular strategies for regenerating oral soft tissue. This review focuses on the efficacy and safety of cell-based investigational approaches to the regeneration of oral soft tissue.

Background and Purpose— Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes. Methods— Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow–derived mesenchymal stem cells (SB623). Results— All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5–10.3; P P P P P Conclusions— In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01287936.

Recurrent ptosis is a common sequel of mastopexy. The use of mesh as an adjunct to the double-skin technique was developed to reduce the incidence of recurrent ptosis. The optimal mesh needs to strike the right balance between persistence, inflammation, biocompatibility, and incorporation without interfering with mammography or presenting a long-term infection risk. This study investigated the ability of a biologic tissue matrix, FortaPerm, to achieve these goals. Women undergoing mastopexy were enrolled in this prospective observational study. The study participants were evaluated at multiple time points for 5 years. Efficacy was assessed primarily by photographic evaluation and secondarily by mammography, patient and physician global assessments, and patient pain assessments. Five women ages 17–41 years were enrolled in this study. At 12 months, 80% of the patients (4/5), and at 5 years, 66% of the patients (2/3) had no asymmetry or ptosis. Mammographic evaluation of the breasts was not affected by the presence of the FortaPerm, and there were no abnormal findings. In two patients, FortaPerm was associated with bilateral seromas associated with extrusion of small amounts of the FortaPerm material in the absence of surrounding inflammation. FortaPerm achieved excellent initial aesthetic outcomes and long-term maintenance of the breast position with no evidence of ptosis 5 years postoperatively for a majority of the patients. FortaPerm did not interfere with mammography, presented no long-term safety concerns, and produced satisfactory results for all patients relative to appearance of the scar as well as shape and firmness of the breasts.

Cell replacement and “bystander” effects of stem cells are currently the widely postulated mechanisms of stem cell-mediated repair. In a recent study, we reported efficacy of modified mesenchymal stromal cell (MSC) transplantation in animal models of traumatic brain injury (TBI), revealing data that corroborate the therapeutic potential of stem cell transplantation for brain injuries, and importantly, evidence that support another mechanism of action of transplanted stem cells. We found that intracerebrally administered SB623 cells (gene-modified human MSCs provided by SanBio Inc.) improved TBI-induced neurobehavioral deficits, via a unique mechanism of action involving the formation of a “biobridge” during the repair phase of TBI. Using immunohistochemistry and laser capture assay, we observed localization of this biobridge in an area between the neurogenic subventricular zone and the injured cortex. This stem cell-paved biobridge expressed high levels of extracellular matrix metalloproteinases (MMPs), which initially co-existed with a stream of transplanted MSCs, and later contained a few to non-detectable grafts and overgrown by newly recruited host cells. We advanced the concept that the biobridge facilitated the long-distance migration of host cells from the neurogenic niche to the injured brain site, representing a key regenerative process that highlights the potential of stem cell grafts to initiate endogenous repair mechanisms. Further studies on elucidating graft-host interaction will likely contribute to in-depth characterization of stem cell-paved biobridge, as a robust brain repair mechanism alongside cell replacement and trophic factor secretion, into a new treatment strategy for TBI and other neurological dysfunctions. In this chapter, we discuss the characteristics of stem cell paved-biobridges, the novel mechanism by which they promote neural repair in a rat model of TBI, and describe the clinical significance, challenges and opportunities of employing this novel stem cell-mediated brain repair concept for the treatment of other neurological disorders beyond TBI.

Peripheral nerve and vascular patterns are congruent in the adult vertebrate, but this has been disputed in vertebrate embryos. The most detailed of these studies have used the avian forelimb as a model system, yet neurovascular anatomical relationships and critical vascular remodeling events remain inadequately characterized in this model. To address this, we have used a combination of intravascular marker injection, multilabel fluorescent stereomicroscopy, and confocal microscopy to analyze the spatiotemporal relationships between peripheral nerves and blood vessels in the forelimb of 818 quail embryos from E2 (HH13) to E15 (HH41). We find that the neurovascular anatomical relationships established during development are highly stereotypic and congruent. Blood vessels typically arise before their corresponding nerves, but there are several critical exceptions to this rule. The vascular pattern is extensively remodeled from the earliest stage examined (E2; HH13), whereas the peripheral nerves, the first of which enter the forelimb at E3.5–E4 (HH21–HH24), have a progressively unfolding pattern that, once formed, remains essentially unchanged. The adult neurovascular pattern is not established until E8 (HH34). Peripheral nerves are always found to track close and parallel to the vasculature. As they track distally, peripheral nerves always lie on the side of the vasculature away from the center of the forelimb. Neurovascular patterns have a hierarchy of congruence that is highest in the dorsoventral plane, followed by the anteroposterior, and lastly the proximodistal planes.

The close spatial relationship between peripheral nerves and blood vessels in the adult is well known. However, evidence supporting the congruent development of these structures in embryos remains anecdotal. Neurovascular relationships also have been shown to be conserved in other vertebrates. This homology suggests that either peripheral nerves or blood vessels, or both, might have fundamental morphogenetic roles during embryologic development. Both peripheral nerves and blood vessels have been independently implicated as etiologic agents in the pathogenesis of congenital disabilities, and several congenital anomalies fit their distribution patterns. This article presents a technique for the simultaneous visualization of peripheral nerves and blood vessels at different stages in the developing embryo. The forelimbs of 310 quail embryos were dissected over a 1-year period. Peripheral nerves were labeled with the neural crest and axon antibody, HNK-1, followed by fluorescein-conjugated secondary antibodies. Blood vessels were labeled by a perfusion technique using the fluorescent dye, dioctadecyl-tetramethylindocarbocyanine. Specimens were processed and imaged in whole-mount with confocal microscopy, and images were reconstructed using three-dimensional modeling software. Both nerves and blood vessels seem to undergo a highly stereotypic sequence of development in the embryonic quail forelimb. Furthermore, the existence of a close spatial relationship between nerves and blood vessels suggests either a high degree of developmental interdependence or shared patterning mechanisms. This technique permits further evaluation of the possible role peripheral nerves and blood vessels might play in the pathogenesis of congenital disabilities and provides a starting point for further studies aimed at elucidating the means by which peripheral nerves and blood vessels are patterned in the forelimb of the avian embryo.

The VACTERL association is an acronym for a constellation of abnormalities affecting the spinal column, anus, heart, trachea, esophagus, kidneys, and limbs that are seen in newborns. It has been shown that prenatal rats exposed to Adriamycin demonstrate a similar series of anomalies. It is the aim of this study to characterize the spectrum of limb anomalies in this model. Female Sprague-Dawley rats (N = 18; 14 experimental and 4 control) were used. After mating, pregnant animals received intraperitoneal injections of Adriamycin (2 mg per kilogram) on days 6, 7, 8, and 9 of gestation. Fetuses were recovered on day 21 of gestation. Ten experimental litters (42 fetuses) and two control litters (18 fetuses) underwent skeletal staining with Alizarin Red S stain. Four experimental litters (N = 18) and two control litters (N = 17) underwent histological study including staining for vascular and neural structures. Upper limb anomalies were found in 45% of the experimental animals, all including either hypoplasia or bending of the radius. The ulna was involved in 37% of the affected limbs. There were no isolated ulnar deformities. There were no histological differences noted. The spectrum of upper limb anomalies seen in the Adriamycin-exposed prenatal rat closely approximates, in incidence and morphology, the upper limb deformities seen with the VACTERL association in children. It is a reliable model for use in additional studies of the embryological mechanism by which these defects arise.

Background: The purpose of the present study was to compare and contrast the clinicopathological features and treatment outcome of chronic sialadenitis involving the parotid and submandibular glands, among patients who were treated by excision of the affected gland. Methods: In a series of 88 patients treated over an 8-year period, 47 had parotid sialadenitis and 41 had submandibular sialadenitis. In the parotid group, 63% of patients were symptomatic for longer than 6 months compared with 27% in the submandibular group. Calculi were implicated in the disease process in 24% of patients with parotid sialadenitis, compared with 73% of patients with submandibular disease. Results: Patients with parotid sialadenitis had superficial (n= 14) or near-total parotidectomy (n= 35), while those with submandibular sialadenitis underwent total gland excision. Complications occurred twice as frequently in the parotidectomy group. The rate of temporary facial nerve weakness was 29% after parotidectomy while marginal mandibular nerve dysfunction occurred after 12% of submandibular excisions. Both procedures were highly effective in permanently relieving the symptoms of sialadenitis. Conclusions: Parotid sialadenitis is infrequently associated with stones and tends to run a longer course before surgical intervention is necessary. Submandibular sialadenitis usually presents earlier, is secondary to calculi and requires early intervention.

Regenerative efforts typically focus on the delivery of single factors, but it is likely that multiple factors regulating distinct aspects of the regenerative process (e.g., vascularization and stem cell activation) can be used in parallel to affect regeneration of functional tissues. This possibility was addressed in the context of ischemic muscle injury, which typically leads to necrosis and loss of tissue and function. The role of sustained delivery, via injectable gel, of a combination of VEGF to promote angiogenesis and insulin-like growth factor-1 (IGF1) to directly promote muscle regeneration and the return of muscle function in ischemic rodent hindlimbs was investigated. Sustained VEGF delivery alone led to neoangiogenesis in ischemic limbs, with complete return of tissue perfusion to normal levels by 3 weeks, as well as protection from hypoxia and tissue necrosis, leading to an improvement in muscle contractility. Sustained IGF1 delivery alone was found to enhance muscle fiber regeneration and protected cells from apoptosis. However, the combined delivery of VEGF and IGF1 led to parallel angiogenesis, reinnervation, and myogenesis; as satellite cell activation and proliferation was stimulated, cells were protected from apoptosis, the inflammatory response was muted, and highly functional muscle tissue was formed. In contrast, bolus delivery of factors did not have any benefit in terms of neoangiogenesis and perfusion and had minimal effect on muscle regeneration. These results support the utility of simultaneously targeting distinct aspects of the regenerative process.

Peripheral nerves and blood vessels have similar patterns in quail forelimb development. Usually, nerves extend adjacent to existing blood vessels, but in a few cases, vessels follow nerves. Nerves have been proposed to follow vascular smooth muscle, endothelium, or their basal laminae. Focusing on the major axial blood vessels and nerves, we found that when nerves grow into forelimbs at E3.5-E5, vascular smooth muscle was not detectable by smooth muscle actin immunoreactivity. Additionally, transmission electron microscopy at E5.5 confirmed that early blood vessels lacked smooth muscle and showed that the endothelial cell layer lacks a basal lamina, and we did not observe physical contact between peripheral nerves and these endothelial cells. To test more generally whether lack of nerves affected blood vessel patterns, forelimb-level neural tube ablations were performed at E2 to produce aneural limbs; these had completely normal vascular patterns up to at least E10. To test more generally whether vascular perturbation affected nerve patterns, VEGF(165), VEGF(121), Ang-1, and soluble Flt-1/Fc proteins singly and in combination were focally introduced via beads implanted into E4.5 forelimbs. These produced significant alterations to the vascular patterns, which included the formation of neo-vessels and the creation of ectopic avascular spaces at E6, but in both under- and overvascularized forelimbs, the peripheral nerve pattern was normal. The spatial distribution of semaphorin3A protein immunoreactivity was consistent with a negative regulation of neural and/or vascular patterning. Semaphorin3A bead implantations into E4.5 forelimbs caused failure of nerves and blood vessels to form and to deviate away from the bead. Conversely, semaphorin3A antibody bead implantation was associated with a local increase in capillary formation. Furthermore, neural tube electroporation at E2 with a construct for the soluble form of neuropilin-1 caused vascular malformations and hemorrhage as well as altered nerve trajectories and peripheral nerve defasciculation at E5-E6. These results suggest that neurovascular congruency does not arise from interdependence between peripheral nerves and blood vessels, but supports the hypothesis that it arises by a shared patterning mechanism that utilizes semaphorin3A. (C) 2003 Elsevier Science (USA). All fights reserved.

Report by John Butler, Specialist Registrar Search checked by , Damien Bates, Specialist Registrar A paramedic crew brings a 27 year old patient with a suspected cervical spine injury to the emergency department after an RTA. At the scene of the accident the patient had full spinal immobilisation, which consisted of a long spinal board, a correctly sized cervical collar, and head blocks with straps to secure …